The long-term objective of the proposed research is to determine the mechanism(s) of maternal to fetal transmission of Human Immunodeficiency Viruses. The SIV system is an ideal model to examine a variety of aspects of HIV pathogenesis. The specific aims of this research are to isolate nd characterize the immunophenotype of rhesus monkey placental cells and determine which of these cells will support Simian Immunodeficiency Virus (SIV) replication. Additionally, the effect of specific cytokines growth factors and anti-HIV drugs will be evaluated to determine their effects on SIV replication in these cells. To accomplish these goals, we will isolate rhesus monkey placental cells during the first, second and third trimester of pregnancy. The cells will then be characterized using variety of means to determine their phenotypes. These cells will be exposed to both cell-associated and free SIV and evaluated for infection. Lastly, specific agents which modulate immunodeficiency virus replication in other cell systems will be added at various times prior to and after SIV infection to determine the effects that these compounds have on SIV replication. These studies will set the stage for the formation of hypotheses regarding transplacental HIV/SIV infection, and a rational evaluation of potential methods for therapeutic intervention in the case of immunodeficiency virus infection during pregnancy.